Prevalence of HPV Infection and p16INK4a Overexpression in Surgically Treated Laryngeal Squamous Cell Carcinoma.

Roberto Gallus,Davide Rizzo,Marco Petrillo,Vincenzo Valentini,Giovanni Delogu,Gian Carlo Mattiucci,Francesco Bussu,Massimo Tommasino,Francesco Miccichè,Dana Holzinger,Damiano Arciuolo,Tarik Gheit,Giampiero Capobianco,Gianluigi Petrone

doi:10.3390/vaccines10020204

Abstract

Background: The mucosal high-risk (HR) human papillomavirus (HPV) is associated with oropharyngeal carcinogenesis. Aims of this study were to evaluate the prevalence of HR-HPV infection in laryngeal squamous cell carcinoma (LSCC) from different subsites, and the clinico-biological meaning of p16 overexpression. Methods: Ninety-seven LSCCs submitted to primary surgery (n = 75) or to post-irradiation salvage laryngectomy (n = 22) were evaluated for HR-HPV DNA and RNA using Luminex-based assays. p16 immunohistochemistry was performed. Results: HR-HPV DNA from HPV16 was detected in seven cases (8.75%), without significant differences between supraglottic and glottic lesions. HPV RNA was never detected. p16 overexpression correlated with HR-HPV DNA, but the kappa agreement score was poor. HPV DNA showed no impact on prognosis. p16 overexpression was associated with a better survival (OS, RFS) in primarily operated cases, while an inverse association with OS was observed in the salvage surgery group. Conclusions: HR-HPV infection appears to have a marginal role in LSCC independent of the anatomical subsite. p16 expression is deregulated in LSCC independent of HPV but displays a prognostic role in patients submitted to primary surgery. The negative predictive role of p16 overexpression in patients undergoing salvage surgery deserves more investigations for validation and elucidation of its clinical relevance.

Highlights

Human papillomaviruses (HPVs) are known to infect cutaneous and mucosal epithelia.Some types of HPV from genus alpha, in particular HPV16, have been associated with many human cancers, i.e., cervical, oropharyngeal, anal, vulvar, and penile [1,2] and are collectively called high-risk human papillomavirus (HR HPV) genotypes
Alcohol consumption correlated with supraglottic site; no other correlation was detected among behavioural risk factors, staging data, HPV DNA, p16 IHC
We evaluated the correlation between p16 IHC and HPV DNA status in the 78 cases where both were available, detecting a significant correlation only when considering as cut-off the composite immunoreactive score of Remmele and Stegner (IRS) score ≥ 4 (p = 0.007 at Likelihood Ratio test) but not when considering the composite IRS score ≥ 6 (p = 0.0733 at Likelihood Ratio test)

Summary

Introduction

Human papillomaviruses (HPVs) are known to infect cutaneous and mucosal epithelia.Some types of HPV from genus alpha, in particular HPV16, have been associated with many human cancers, i.e., cervical, oropharyngeal, anal, vulvar, and penile [1,2] and are collectively called high-risk human papillomavirus (HR HPV) genotypes. The role of HPV in laryngeal carcinogenesis, postulated back in the 1980s [5], is less prominent than in other sites and is not currently considered clinically relevant [6,7]. In. The mucosal high-risk (HR) human papillomavirus (HPV) is associated with oropharyngeal carcinogenesis. Aims of this study were to evaluate the prevalence of HR-HPV infection in laryngeal squamous cell carcinoma (LSCC) from different subsites, and the clinico-biological meaning of p16 overexpression. Conclusions: HR-HPV infection appears to have a marginal role in LSCC independent of the anatomical subsite. P16 expression is deregulated in LSCC independent of HPV but displays a prognostic role in patients submitted to primary surgery. The negative predictive role of p16 overexpression in patients undergoing salvage surgery deserves more investigations for validation and elucidation of its clinical relevance

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